miR-375 maintains normal pancreatic alpha- and beta-cell mass.

Journal article

Altered growth and development of the endocrine pancreas is a frequent cause of the hyperglycemia associated with diabetes. Here we show that microRNA-375 (miR-375), which is highly expressed in pancreatic islets, is required for normal glucose homeostasis. Mice lacking miR-375 (375KO) are hyperglycemic, exhibit increased total pancreatic alpha-cell numbers, fasting and fed plasma glucagon levels, and increased gluconeogenesis and hepatic glucose output. Furthermore, pancreatic beta-cell mass is decreased in 375KO mice as a result of impaired proliferation. In contrast, pancreatic islets of obese mice (ob/ob), a model of increased beta-cell mass, exhibit increased expression of miR-375. Genetic deletion of miR-375 from these animals (375/ob) profoundly diminished the proliferative capacity of the endocrine pancreas and resulted in a severely diabetic state. Bioinformatic analysis of transcript data from 375KO islets revealed that miR-375 regulates a cluster of genes controlling cellular growth and proliferation. These data provide evidence that miR-375 is essential for normal glucose homeostasis, alpha- and beta-cell turnover, and adaptive beta-cell expansion in response to increasing insulin demand in insulin resistance.

Authors: Poy, M; Hausser, J; Trajkovski, M; Braun, M; Collins, S

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 106
• Issue: 14
• Pages: 5813-5818
• Publication date: 2009-04-01
• DOI: 10.1073/pnas.0810550106
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Insulin; Homeostasis; Mice; Blood Glucose; Glucagon-Secreting Cells; Insulin-Secreting Cells; Animals; MicroRNAs; Islets of Langerhans; Cell Proliferation; Mice, Knockout; Mice, Obese